Triethylamine → tert-butyl (6R,7R)-7-(3,4-dichlorophenyl)-6-{[4-(ethoxycarbonyl)-1,3-thiazol-2-yl]methyl}-1,4-oxazepane-4-carboxylate

HRID 1022710Notes

Reaction equation

HRID 1022710 reaction equation
Br[CH2:2][C:3](=O)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[NH2:10][C:11](=[S:35])[CH2:12][C@H:13]1[C@H:19]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[O:18][CH2:17][CH2:16][N:15]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:14]1.C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(=O)([O-])O.[Na+]>CCO>[Cl:27][C:22]1[CH:21]=[C:20]([C@@H:19]2[O:18][CH2:17][CH2:16][N:15]([C:28]([O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:29])[CH2:14][C@H:13]2[CH2:12][C:11]2[S:35][CH:2]=[C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[N:10]=2)[CH:25]=[CH:24][C:23]=1[Cl:26]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 66144Ethyl bromopyruvateHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 86663871tert-butyl (6R,7R)-6-(2-amino-2-thioxoethyl)-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate

Product 1

HCID 66975587tert-butyl (6R,7R)-7-(3,4-dichlorophenyl)-6-{[4-(ethoxycarbonyl)-1,3-thiazol-2-yl]methyl}-1,4-oxazepane-4-carboxylateYield 101.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl bromopyruvate (0.070 mL, 0.50 mmol) was added to a solution of tert-butyl (6R,7R)-6-(2-amino-2-thioxoethyl)-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate (140 mg, 0.33 mmol) in EtOH (5 mL). The reaction mixture was stirred at 80° C. for 2 hr, triethylamine (0.140 mL, 1.00 mmol) and di-tert-butyl dicarbonate (0.115 mL, 0.50 mmol) were added at room temperature, and the mixture was stirred at room temperature for 5 hr. To the reaction mixture was added aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (173 mg).

Workup

  1. stirringthe mixture was stirred at room temperature for 5 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a618fcce9a1f4c5d9e850331cb546ed3
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

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